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1.
Med Image Anal ; 97: 103243, 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38954941

ABSTRACT

Instance segmentation of biological cells is important in medical image analysis for identifying and segmenting individual cells, and quantitative measurement of subcellular structures requires further cell-level subcellular part segmentation. Subcellular structure measurements are critical for cell phenotyping and quality analysis. For these purposes, instance-aware part segmentation network is first introduced to distinguish individual cells and segment subcellular structures for each detected cell. This approach is demonstrated on human sperm cells since the World Health Organization has established quantitative standards for sperm quality assessment. Specifically, a novel Cell Parsing Net (CP-Net) is proposed for accurate instance-level cell parsing. An attention-based feature fusion module is designed to alleviate contour misalignments for cells with an irregular shape by using instance masks as spatial cues instead of as strict constraints to differentiate various instances. A coarse-to-fine segmentation module is developed to effectively segment tiny subcellular structures within a cell through hierarchical segmentation from whole to part instead of directly segmenting each cell part. Moreover, a sperm parsing dataset is built including 320 annotated sperm images with five semantic subcellular part labels. Extensive experiments on the collected dataset demonstrate that the proposed CP-Net outperforms state-of-the-art instance-aware part segmentation networks.

2.
Adv Biol (Weinh) ; : e2300678, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38837283

ABSTRACT

This study focuses on the role of topoisomerases (TOPs) in sarcomas (SARCs), highlighting TOPs' influence on sarcoma prognosis through mRNA expression, genetic mutations, immune infiltration, and DNA methylation analysis using transcriptase sequencing and other techniques. The findings indicate that TOP gene mutations correlate with increased inflammation, immune cell infiltration, DNA repair abnormalities, and mitochondrial fusion genes alterations, all of which negatively affect sarcoma prognosis. Abnormal TOP expression may independently affect sarcoma patients' survival. Cutting-edge genomic tools such as Oncomine, gene expression profiling interactive analysis (GEPIA), and cBio Cancer Genomics Portal (cBioPortal) are utilized to explore the TOP gene family (TOP1/1MT/2A/2B/3A/3B) in soft-tissue sarcomas (STSs). This in-depth analysis reveals a notable upregulation of TOP mRNA in STS patients arcoss various SARC subtypes, French Federation Nationale des Centres de Lutte Contre le Cancer classification (FNCLCC) grades, and specific molecular profiles correlating with poorer clinical outcomes. Furthermore, this investigation identifies distinct patterns of immune cell infiltration, genetic mutations, and somatic copy number variations linked to TOP genes that inversely affect patient survival rates. These findings underscore the diagnostic and therapeutic relevance of the TOP gene suite in STSs.

3.
Reprod Biol Endocrinol ; 22(1): 59, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38778327

ABSTRACT

BACKGROUND: Deep learning has been increasingly investigated for assisting clinical in vitro fertilization (IVF). The first technical step in many tasks is to visually detect and locate sperm, oocytes, and embryos in images. For clinical deployment of such deep learning models, different clinics use different image acquisition hardware and different sample preprocessing protocols, raising the concern over whether the reported accuracy of a deep learning model by one clinic could be reproduced in another clinic. Here we aim to investigate the effect of each imaging factor on the generalizability of object detection models, using sperm analysis as a pilot example. METHODS: Ablation studies were performed using state-of-the-art models for detecting human sperm to quantitatively assess how model precision (false-positive detection) and recall (missed detection) were affected by imaging magnification, imaging mode, and sample preprocessing protocols. The results led to the hypothesis that the richness of image acquisition conditions in a training dataset deterministically affects model generalizability. The hypothesis was tested by first enriching the training dataset with a wide range of imaging conditions, then validated through internal blind tests on new samples and external multi-center clinical validations. RESULTS: Ablation experiments revealed that removing subsets of data from the training dataset significantly reduced model precision. Removing raw sample images from the training dataset caused the largest drop in model precision, whereas removing 20x images caused the largest drop in model recall. by incorporating different imaging and sample preprocessing conditions into a rich training dataset, the model achieved an intraclass correlation coefficient (ICC) of 0.97 (95% CI: 0.94-0.99) for precision, and an ICC of 0.97 (95% CI: 0.93-0.99) for recall. Multi-center clinical validation showed no significant differences in model precision or recall across different clinics and applications. CONCLUSIONS: The results validated the hypothesis that the richness of data in the training dataset is a key factor impacting model generalizability. These findings highlight the importance of diversity in a training dataset for model evaluation and suggest that future deep learning models in andrology and reproductive medicine should incorporate comprehensive feature sets for enhanced generalizability across clinics.


Subject(s)
Deep Learning , Spermatozoa , Humans , Pilot Projects , Male , Spermatozoa/physiology , Fertilization in Vitro/methods , Image Processing, Computer-Assisted/methods , Semen Analysis/methods
4.
ACS Omega ; 9(10): 11958-11968, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38496998

ABSTRACT

Aluminum is a metal element with significant neurotoxicity, and there is a substantial correlation between aluminum exposure and cognitive dysfunction. Glial fibrillary acidic protein (GFAP) is widely used as a marker of reactive astrocyte proliferation in response to pathological injury of the central nervous system. Studies of various neurodegenerative diseases have confirmed that the expression changes in GFAP are associated with nerve injury. We investigated the role of LNC000152 in the aluminum-induced reactive proliferation of astrocytes. By establishing two aluminum-exposed cell models of rat primary astrocytes and CTX-TNA2 cell lines, we examined the expression of LNC000152 and GFAP and detected cell proliferation with EdU and cell cycle changes with flow cytometry. The role of aluminum in promoting glial cell proliferation was verified; the expression levels of LNC000152 and GFAP increased with the concentration of aluminum exposure. Intervention of LNC000152 expression by siRNA technology revealed that LNC000152 affected glial cell responsive proliferation by influencing GFAP expression. These results suggest that LNC000152 plays a role in the reactive proliferation of astrocytes induced by aluminum.

5.
Ying Yong Sheng Tai Xue Bao ; 35(2): 543-554, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38523113

ABSTRACT

Under the context of global climate change and growing population, irrigation and fertilization have become important ways to ensure food production, with consequences on water cycling, energy flow, and materials cycling in terrestrial ecosystems. In the land surface model (LSM), coupling irrigation and fertilization schemes are of great importance for clearly understanding the land-atmosphere interactions to ensure food security. We reviewed the expression methods of three key parameters, namely, the applied method, usage, and time in the parameterization process of irrigation and fertilization (nitrogen fertilizer) in LSM. We found that the ways to irrigate and ferti-lize in LSM are different from the ways used in actual practice due to the limitation of the high resolution of spatio-temporal data, which makes it difficult to understand the actual influences of irrigation and fertilization on grain yield, environment, and local climate. Finally, we proposed future works: 1) taking the differences of crop water demand into account and making the different irrigation thresholds for different crops to properly evaluate the total and intensity of water consumption of different crops; 2) using the field records and the regional grid data of fertilization and irrigation developed in recent years to develop parameterized schemes that are more in line with actual agricultural operations, which can accurately reveal their economic, ecological, and climatic effects; 3) developing fertilization diagnosis scheme considering crop type, phenological stage, and soil basic fertility as the supplementary scheme in LSM, to improve the applicability and simulation accuracy of LSM in the areas without nitrogen fertilizer data.


Subject(s)
Agricultural Irrigation , Fertilizers , Agricultural Irrigation/methods , Agriculture/methods , Ecosystem , Nitrogen/analysis , Soil , Water
6.
Mol Ther Nucleic Acids ; 35(1): 102137, 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38384444

ABSTRACT

Decoy oligodeoxynucleotides (ODNs) allow targeting undruggable transcription factors, such as STAT3, but their limited potency and lack of delivery methods hampered translation. To overcome these challenges, we conjugated a STAT3-specific decoy to thalidomide, a ligand to cereblon in E3 ubiquitin ligase complex, to generate a proteolysis-targeting chimera (STAT3DPROTAC). STAT3DPROTAC downregulated STAT3 in target cells, but not STAT1 or STAT5. Computational modeling of the STAT3DPROTAC ternary complex predicted two surface lysines, K601 and K626, in STAT3 as potential ubiquitination sites. Accordingly, K601/K626 point mutations in STAT3, as well as proteasome inhibition or cereblon deletion, alleviated STAT3DPROTAC effect. Next, we conjugated STAT3DPROTAC to a CpG oligonucleotide targeting Toll-like receptor 9 (TLR9) to generate myeloid/B cell-selective C-STAT3DPROTAC. Naked C-STAT3DPROTAC was spontaneously internalized by TLR9+ myeloid cells, B cells, and human and mouse lymphoma cells but not by T cells. C-STAT3DPROTAC effectively decreased STAT3 protein levels and also STAT3-regulated target genes critical for lymphoma cell proliferation and/or survival (BCL2L1, CCND2, and MYC). Finally, local C-STAT3DPROTAC administration to human Ly3 lymphoma-bearing mice triggered tumor regression, while control C-STAT3D and C-SCR treatments had limited effects. Our results underscore the feasibility of using a PROTAC strategy for cell-selective, decoy oligonucleotide-based STAT3 targeting of and potentially other tumorigenic transcription factors for cancer therapy.

7.
J Affect Disord ; 351: 449-457, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38296060

ABSTRACT

BACKGROUND: Insomnia is very common in psychiatric disorders, but the polysomnographic (PSG) characteristics of insomnia in various psychiatric disorders are still not agreed upon. This study aimed to investigate the characteristics of PSG and its relationship with metabolic indicators in insomnia patients with affective disorders and primary insomnia (PI) patients. METHODS: A total of 38 patients with PI, 44 major depressive disorder patients with insomnia (DI), 49 generalized anxiety disorder patients with insomnia (GI), and 19 bipolar mania patients with insomnia (BI) were included. PSG was used to detect sleep problems in subjects, and biochemical indicators were also collected. RESULTS: The results of this study found that subjects with BI were lower on REM sleep latency (RL), awakenings number (AN), number of microarousals (NM), and apnea-hypopnea index (AHI) than those with DI and GI, and lower on RL and AN than those with PI. Subjects with PI had lower NM and AHI than those with DI and GI. Patients with DI had a higher RL than those with GI. All results passed Bonferroni correction (p < 0.00078). No differences in biochemical indices were found among the four groups of subjects. Also, AHI was found to be positively correlated with free triiodothyronine (FT3) and fasting blood glucose in subjects. CONCLUSION: This study suggests that various psychiatric disorders may have their characteristics in terms of PSG parameters, which prompted us to focus on the PSG characteristics of these disorders when assessing them, as well as to focus on their biochemical indicators.


Subject(s)
Bipolar Disorder , Depressive Disorder, Major , Sleep Initiation and Maintenance Disorders , Humans , Sleep Initiation and Maintenance Disorders/complications , Depressive Disorder, Major/complications , Depressive Disorder, Major/diagnosis , Bipolar Disorder/complications , Mania , Polysomnography , Anxiety Disorders/complications , Anxiety Disorders/diagnosis
8.
Food Funct ; 15(3): 1720, 2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38226873

ABSTRACT

Correction for 'Wheat peptides inhibit the activation of MAPK and NF-κB inflammatory pathways and maintain epithelial barrier integrity in NSAID-induced intestinal epithelial injury' by Zhiyuan Feng et al., Food Funct., 2024, https://doi.org/10.1039/D3FO03954D.

9.
Res Child Adolesc Psychopathol ; 52(1): 93-110, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37405589

ABSTRACT

Inhibitory control is a transdiagnostic risk factor for externalizing behaviors, particularly during adolescence. Despite advances in understanding links between inhibitory control and externalizing behaviors across youth on average, significant questions remain about how these links play out in the day-to-day lives of individual adolescents. The goals of the current study were to: (1) validate a novel 100-occasion measure of inhibitory control; (2) assess links between day-to-day fluctuations in inhibitory control and individual differences in externalizing behaviors; and (3) illustrate the potential of intensive longitudinal studies for person-specific analyses of adolescent externalizing behaviors. Participants were 106 youth (57.5% female, Mage = 13.34 years; SDage = 1.92) who completed a virtual baseline session followed by 100 daily surveys, including an adapted Stroop Color Word task designed to assess inhibitory control. Results suggested that the novel task was generally reliable and valid, and that inhibitory control fluctuated across days in ways that were meaningfully associated with individual differences in baseline impulsive behaviors. Results of illustrative personalized analyses suggested that inhibitory control had more influence in the daily networks of adolescents who used substances during the 100 days than in a matched set of adolescents who did not. This work marks a path forward in intensive longitudinal research by validating a novel inhibitory control measure, revealing that daily fluctuations in inhibitory control may be a unique construct broadly relevant to adolescent externalizing problems, and at the same time, highlighting that links between daily inhibitory control and impulsive behaviors are adolescent-specific.


Subject(s)
Adolescent Behavior , Humans , Adolescent , Female , Male , Impulsive Behavior , Longitudinal Studies , Individuality , Surveys and Questionnaires
10.
Food Funct ; 15(2): 823-837, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38131381

ABSTRACT

The use of non-steroidal anti-inflammatory drugs (NSAIDs) has negative effects on the gastrointestinal tract, but the proton pump inhibitors currently in use only protect against gastrointestinal disease and may even make NSAID-induced enteropathy worse. Therefore, new approaches to treating enteropathy are required. This study aimed to investigate the protective effect of wheat peptides (WPs) against NSAID-induced intestinal damage in mice and their mechanism. Here, an in vivo mouse model was built to investigate the protective and reparative effects of different concentrations of WPs on NSAID-induced intestinal injury. WPs ameliorated NSAID-induced weight loss and small intestinal tissue damage in mice. WP treatment inhibited NSAID-induced injury leading to increased levels of oxidative stress and expression levels of inflammatory factors. WPs protected and repaired the integrity and permeability injury of the intestinal tight junction induced by NSAIDs. An in vitro Caco-2 cell model was built with lipopolysaccharide (LPS). WP pretreatment inhibited LPS-induced changes in the Caco-2 cell permeability and elevated the levels of oxidative stress. WPs inhibited LPS-induced phosphorylation of NF-κB p65 and mitogen-activated protein kinase (MAPK) signaling pathways and reduced the expression of inflammatory factors. In addition, WPs increased tight junction protein expression, which contributed to improved intestinal epithelial dysfunction. Our results suggest that WPs can ameliorate NSAID-induced impairment of intestinal barrier functional integrity by improving intestinal oxidative stress levels and reducing inflammatory factor expression through inhibition of NF-κB p65 and MAPK signaling pathway activation. WPs can therefore be used as potential dietary supplements to reduce NSAID-induced injury of the intestine.


Subject(s)
Gastrointestinal Diseases , Intestinal Diseases , Humans , Mice , Animals , NF-kappa B/genetics , NF-kappa B/metabolism , Mitogen-Activated Protein Kinases/metabolism , Triticum/metabolism , Caco-2 Cells , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Lipopolysaccharides/pharmacology , Intestinal Diseases/metabolism , Peptides/pharmacology , Peptides/metabolism , Intestinal Mucosa/metabolism
11.
Int J Biol Macromol ; 258(Pt 1): 128948, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38143056

ABSTRACT

The ideal hemostatic agents should be able to stop bleeding quickly and avoid secondary bleeding caused by adhesion with blood clots during dressing change. Herein, a hydrophobic electrospun nanofiber membrane was prepared for achieving hemostasis, rationally targeting both attributes, via doping N-alkylated chitosan (N-CS) grafted with octadecyl into chitosan/polyethylene oxide (PEO). In vitro and in vivo coagulation tests showed that CPNs doped with small amounts of N-CS (CPN31) could significantly shorten hemostasis time and promote the formation of more stable and stronger blood clots. In particular, the whole blood clotting time of CPN31 (58.8 ± 2.2 s) was significantly lower than that of chitosan/PEO (CPN0) nanofiber membrane (67 ± 3.5 s) and the medical sterile gauze (86.7 ± 0.6 s). Furthermore, due to the hemophobic nature of CPNs, blood wetting of the dressing was severely limited and blood can coagulated at the site of liver injury in rats, thus reducing blood loss and allowing rapid removal of the dressing without triggering secondary hemorrhage. The CPN31 exhibited excellent hemostasis properties, easy to remove, blood compatibility, biocompatibility and promoting fibroblast proliferation properties. This hydrophobic CPNs is a promising biological adhesive for hemorrhage control.


Subject(s)
Chitosan , Hemostatics , Nanofibers , Thrombosis , Rats , Animals , Chitosan/chemistry , Polyethylene Glycols/pharmacology , Nanofibers/chemistry , Hemostasis , Hemostatics/chemistry , Hemorrhage , Liver
12.
Ecotoxicol Environ Saf ; 270: 115860, 2024 Jan 15.
Article in English | MEDLINE | ID: mdl-38142589

ABSTRACT

Epidemiological studies from diverse global regions suggest a correlation between the accumulation of aluminum in the brain and the onset of various neurodegenerative diseases, including Alzheimer's disease, of which, neuronal cells death happen. Our previous research has found the potential of aluminum to induce neuronal cell death. A comprehensive exploration of the regulatory pathways influenced by aluminum in neuronal cell death could contribute to the development of strategies aimed at preventing the detrimental impact of aluminum on neuronal cells. This study is dedicated to exploring the impact of aluminum on mitochondrial homeostasis through the RIP3-PGAM5-Drp1 pathway, with a specific focus on its potential role in necroptosis. We observed that the inhibition of RIP3 function and the reduction in PGAM5 protein expression both mitigate aluminum-induced necroptosis in PC12 cells and enhance mitochondrial function. However, the inhibition of PGAM5 protein expression does not exert an impact on the expression of RIP3 and MLKL proteins. In summary, our study posits that aluminum can induce necroptosis in PC12 cells through the RIP3-PGAM5-Drp1 pathway.


Subject(s)
Aluminum , Apoptosis , Rats , Animals , PC12 Cells , Aluminum/toxicity , Aluminum/metabolism , Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases/genetics
13.
Plant Physiol Biochem ; 203: 107996, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37688900

ABSTRACT

Volatile esters are the main aromatic components that affect consumer sensory preferences. Aroma is a crucial characteristic of the 'Nanguo' pear (Pyrus ussriensis Maxim). Carboxylesterases (CXEs) are positively correlated with the catabolism of volatile esters in peaches; however, the mechanism of action of CXE family members in 'Nanguo' pear is poorly understood. In this study, 40 PuCXEs were identified in the 'Nanguo' pear and assigned into seven groups. In addition, we found that most PuCXEs were relatively conserved and contained cytoplasmic proteins. This hypothesis was supported by phylogenetic analysis, investigation of conserved domains and gene structures, and prediction of subcellular localization. Based on the content of volatile esters and expression levels of PuCXEs analysis, four PuCXEs, including PuCXE7, PuCXE15, PuCXE20, and PuCXE25, had a significant negative correlation with volatile ester accumulation. Particularly, the correlation of PuCXE15 far exceeded that of the other PuCXEs. The results of the transient expression assay showed that PuCXE15 promoted the degradation of ester in vivo. Subcellular localization experiment revealed that PuCXE15 is located in the plasma membrane and nucleus. These results show that PuCXE15 functions in the catabolism of volatile ester in 'Nanguo' pear fruit, and provides a foundation for enhancing aroma quality by artificial control in pear.

14.
Prev Med Rep ; 35: 102396, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37705881

ABSTRACT

Parent's nutrition knowledge, attitudes, and dietary practices (KAP) play imperative roles in preventing malnutrition for themselves and their children. Our study aimed to determine the status and contributing factors of nutrition KAP among parents of children and adolescents. A total of 1746 parents (mean age 39.67 ± 5.38 years, females accounting for 69.82%) of primary and junior high school students in Weifang, China, completed a self-reported KAP questionnaire in August 2021. An analysis of Pearson product-moment correlation was conducted to determine the relationship between knowledge, attitudes, and practices. Chi-square test, followed by a multivariable robust Poisson regression analysis, was performed to identify the contributing factors to parents' KAP. A 65.94% awareness rate of nutritional knowledge was observed. The correlations between nutrition knowledge and attitudes (r = 0.03, P = 0.23), knowledge and practices (r = 0.02, P = 0.34), and attitudes and practices (r = 0.16, P < 0.01) were relatively weak. After adjusting for other contributing factors, females [prevalence ratio (PR) = 1.28, 95% confidence interval (CI) = 1.13-1.45], participants with secondary education (PR = 4.64, 95% CI = 1.60-13.50), junior college education (PR = 5.87, 95% CI = 2.01-17.13) and college degree or above education (PR = 6.58, 95% CI = 2.25-19.23) acquired higher nutrition knowledge scores. Moreover, healthy diet behaviors were more commonly implemented by females than males (PR = 1.42, 95% CI = 1.14-1.76), and which needed to be improved in those with abnormal body mass indexes (BMIs) [overweight (PR = 0.86, 95% CI = 0.74-0.99) and obese (PR = 0.76, 95% CI = 0.56-0.99)]. It was necessary for nutrition KAP promotion to be emphasized in nutritional knowledge and dietary practices, as well as health behavior guidance, especially for parents with low education and elevated BMIs.

15.
Biosens Bioelectron ; 241: 115688, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37714062

ABSTRACT

Traditional lateral flow immunoassays (LFIA) suffer from insufficient sensitivity, difficulty for quantitation, and susceptibility to complex substrates, limiting their practical application. Herein, we developed a polyethylenimine (PEI)-mediated approach for assembling high-density Au nanoshells onto Fe3O4 nanoclusters (MagAushell) as LFIA labels for integrated enrichment and photothermal/colorimetric dual-mode detection of SARS-CoV-2 nucleocapsid protein (N protein). PEI layer served not only as "binders" to Fe3O4 nanoclusters and Au nanoshells, but also "barriers" to ambient environment. Thus, MagAushell not only combined magnetic and photothermal properties, but also showed good stability. With MagAushell, N protein was first separated and enriched from complex samples, and then loaded to the strip for detection. By observation of the color stripes, qualitative detection was performed with naked eye, and by measuring the temperature change under laser irradiation, quantification was attained free of sophisticated instruments. The introduction of Fe3O4 nanoclusters facilitated target purification and enrichment before LFIA, which greatly improved the anti-interference ability and increased the detection sensitivity by 2 orders compared with those without enrichment. Moreover, the high loading density of Au nanoshells on one Fe3O4 nanocluster enhanced the photothermal signal of the nanoprobe significantly, which could further increase the detection sensitivity. The photothermal detection limit reached 43.64 pg/mL which was 1000 times lower than colloidal gold strips. Moreover, this method was successfully applied to real samples, showing great application potential in practice. We envision that this LFIA could serve not only for SARS-CoV-2 detection but also as a general test platform for other biotargets in clinical samples.


Subject(s)
Biosensing Techniques , COVID-19 , Metal Nanoparticles , Nanoshells , Humans , SARS-CoV-2 , Colorimetry , COVID-19/diagnosis , Nucleocapsid Proteins , Immunoassay , Metal Nanoparticles/chemistry
16.
bioRxiv ; 2023 Aug 03.
Article in English | MEDLINE | ID: mdl-37577590

ABSTRACT

Decoy-oligodeoxynucleotides (D-ODNs) can target undruggable transcription factors, such as STAT3. However, challenges in D-ODN delivery and potency hampered their translation. To overcome these limitations, we conjugated STAT3-specific D-ODN to thalidomide (Tha), a known ligand to cereblon (CRBN, a component of E3 ubiquitin ligase) to generate a proteolysis-targeting chimera (STAT3D PROTAC ). STAT3D PROTAC downregulated STAT3, but not STAT1 or STAT5, in target cells. Computational modeling of the STAT3D PROTAC ternary complex predicted two surface lysines on STAT3, K601 and K626 as potential ubiquitination sites for the PROTAC bound E3 ligase. Accordingly, K601/K626 point mutations in STAT3, as well as proteasome inhibitors, and CRBN deletion alleviated STAT3D PROTAC effect. Next, we conjugated STAT3D PROTAC to a CpG ligand targeting Toll-like receptor 9 (TLR9) to generate myeloid/B-cell-selective C-STAT3D PROTAC conjugate. Naked C-STAT3D PROTAC was spontaneously internalized by TLR9 + myeloid cells, B cells as well as human Ly18 and mouse A20 lymphoma cells, but not by T cells. C-STAT3D PROTAC decreased STAT3 levels to 50% at 250 nM and over 85% at 2 µM dosing in myeloid cells. We also observed significantly improved downregulation of STAT3 target genes involved in lymphoma cell proliferation and/or survival ( BCL2L1, CCND2, MYC ). Finally, we assessed the antitumor efficacy of C-STAT3D PROTAC compared to C-STAT3D or scrambled control (C-SCR) against human lymphoma xenotransplants. Local C-STAT3D PROTAC administration triggered lymphoma regression while control treatments had limited effects. Our results underscore feasibility of using PROTAC strategy for cell-selective, decoy oligonucleotide-based targeting of STAT3 and potentially other tumorigenic transcription factors for cancer therapy.

17.
Children (Basel) ; 10(7)2023 Jul 21.
Article in English | MEDLINE | ID: mdl-37508750

ABSTRACT

BACKGROUND: In China, sleep disorders have become a public health concern. This study aimed to model the relationship between adverse events and sleep quality, as well as the effect of group step aerobics on sleep quality. METHODS: The modeling was built on surveying 2760 16-19-year-old adolescents. The Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality, and the Adolescent Self-rating Life Events Checklist (ASLEC) was used to evaluate adverse events. Adolescents with sleep disorders (PSQI ≥ 8) were randomized into the control (n = 26) and exercise (n = 26) groups. The exercise group participated in 12-week step aerobics, and the 300 min weekly volume is compliant with the WHO physical activity guidelines. RESULTS: The double Poisson distribution was chosen to fit the data. ASLEC had a nonlinear relationship with the PSQI. Participants in the exercise group slept better (p < 0.05) from the eighth week until the end of the study. A random adolescent, therefore, has a 92.5% probability of experiencing improved sleep quality after 12 weeks of step aerobics. CONCLUSIONS: Intervention should be implemented before adverse events accumulate. An active lifestyle should be a preparedness strategy for increasing the resilience of adolescent mental health in the face of adversity.

18.
Front Nutr ; 10: 1140191, 2023.
Article in English | MEDLINE | ID: mdl-37305088

ABSTRACT

In the food processing field, it is very often that fish proteins are denatured affecting the nutritional value of the product which is vital to be solved. By using appropriate sugar donors for glycosylation with protein, improving the stability and emulsification properties of fish proteins can be achieved. This research looks into the impacts of enzymatic chitosan oligosaccharide (CO) at various concentration (0.15%, 0.30%, 0.45%, 0.60%, w/v) upon the molecular makeup and function of silver carp myofibrillar protein (MP) in an attempt to comprehend the impact of electrostatic binding among MP as well as CO on protein conformation. Analysis was done on the impact of various CO concentrations upon MP's secondary structure, conformational changes, and functional characteristics. Twelve sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) assays were implemented to monitor MP; Fourier transform infrared spectroscopy, endogenous fluorescence spectroscopy, and UV absorption spectra were carried out to investigate the influence of CO on MP; Particle size distribution, emulsifying activity index (EAI), solubility, turbidity, sulfhydryl content, carbonyl content, foaming capacity, surface hydrophobicity, emulsifying stability index (ESI), and foam persistence were all investigated. In addition, we used dynamic light scattering, scanning electron microscope, and atomic force microscope to analyze myosin (MO) and 0.60% CO-MO complex. The results demonstrated that CO and MP form complexes through hydrogen bonding and electrostatic interactions. CO modification not only delayed the oxidation of MP but also promoted MP to show better solubility, foaming, and foaming stability. In addition, CO modified myosin particle size decreased, reducing myosin's roughness and making myosin's structure more compact. To sum up, molecular interaction could change functional characteristics, and products with special properties could be developed after modification with chitosan oligosaccharide.

19.
ACS Omega ; 8(24): 21823-21829, 2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37360444

ABSTRACT

Catalytic ozonation is an effective and promising advanced oxidation technology for organic pollutant removal. Herein, CexMn1-xO2 metal oxides loaded on Al2O3 catalysts (Mn-Ce/Al2O3) were synthesized for catalytic ozonation of the wastewater containing ciprofloxacin. The morphology, crystal structure, and specific surface area of the prepared catalyst were characterized. The characteristics of the Mn-Ce/Al2O3 catalyst revealed that the loaded MnO2 could interfere with the formed CeO2 crystals and then produced complex CexMn1-xO2 oxides. Compared with an ozone-alone system (47.4%), the ciprofloxacin degradation efficiency in the Mn-Ce/Al2O3 catalytic ozonation system elevated to 85.1% within 60 min. The ciprofloxacin degradation kinetic rate over the Mn-Ce/Al2O3 catalyst is 3.0 times that of the ozone-alone system. The synergetic corporation of redox pairs between Mn(III)/Mn(IV) and Ce(III)/Ce(IV) in the Mn-Ce/Al2O3 catalyst could accelerate ozone decomposition to generate active oxygen species and further significantly improve the mineralization efficiency of ciprofloxacin. The work demonstrates the great potential of developing dual-site ozone catalysts for advanced treatment of wastewater.

20.
J Colloid Interface Sci ; 645: 986-996, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37179196

ABSTRACT

Autophagy inducers increase the sensitivity of tumor cells to chemotherapeutic drugs and enhance anti-tumor efficacy. An autophagy-induced intracellular signaling fractional nano-drug system was constructed for the co-delivery of the autophagy inducer rapamycin (RAPA) and the anti-tumor drug 9-nitro-20(S)-camptothecin (9-NC). Link peptides, including cathepsin B-sensitive peptides (Ala-Leu-Ala-Leu, ALAL), nucleus-targeting peptides (TAT, sequence: YGRKKRRQRRR), and chrysin (CHR)-modified hydrophobic biodegradable polymers (poly(-caprolactone)) (PCL), were grafted onto hyaluronic acid (HA) to yield two amphiphiles, HA-ALAL-PCL-CHR (CPAH) and HA-ALAL-TAT-PCL-CHR (CPTAH). Spherical RAPA- and 9-NC-loaded micelles were obtained by the self-assembly of amphiphiles comprising CPAH and RAPA and CPTAH and 9-NC. In this fractional nano-drug system, RAPA was released earlier than 9-NC, as CPAH as a RAPA carrier lacked a nucleus-targeting TAT (unlike CPTAH as an 9-NC carrier). RAPA induced autophagy in tumor cells and improved their sensitivity, whereas the secondary nucleus-targeting micelles directly delivered 9-NC to the nucleus, considerably improving anti-tumor efficacy. Immunofluorescence staining, acridine orange (AO) staining, and western blotting results demonstrated that the system induced a high level of autophagy in combination chemotherapy. The proposed system possesses a high level of cytotoxicity in vitro and in vivo and provides a potential method for enhancing anti-tumor efficacy in clinical settings.


Subject(s)
Antineoplastic Agents , Nanoparticles , Neoplasms , Humans , Micelles , Antineoplastic Agents/chemistry , Sirolimus/pharmacology , Sirolimus/therapeutic use , Neoplasms/drug therapy , Neoplasms/pathology , Drug Carriers/chemistry , Peptides/pharmacology , Nanoparticles/therapeutic use , Autophagy , Cell Line, Tumor
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